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Genome Biology 2005, 6:336 comment reviews reports deposited research interactions information refereed research Meeting report Fungal biology reaps the benefit of genomics Ralph Dean, Thomas Mitchell, Nicole Donofrio, Jun-Seop Jeong and Amy Powell Address: Center for Integrated Fungal Research, Department of Plant Pathology, North Carolina State University, Raleigh, NC 27606, USA. Correspondence: Ralph Dean. E-mail: Ralph_Dean@ncsu.edu Published: 28 July 2005 Genome Biology 2005, 6:336 (doi:10.1186/gb-2005-6-8-336) The electronic version of this article is the complete one and can be found online at http://genomebiology.com/2005/6/8/336 © 2005 BioMed Central Ltd A report on the 23rd Fungal Genetics Conference, Pacific Grove, USA, 15-20 March 2005. Earlier this year more than 700 fungal biologists from around the world, studying everything from yeast to sapro- phytes, pathogens, and endophytes, made their biennial spring pilgrimage to California for the 23rd Fungal Genetics Conference, where the breadth of fungal biology, evolution, pathogenesis, and reproduction was discussed. Research presented at this year’s conference generated a level of energy and excitement not seen in recent memory, stem- ming from the explosion in the number of fungal genomes with full or partial sequence coverage since the previous meeting in 2003. This avalanche of genome sequence data has drastically changed the landscape of fungal research, and in many respects provides future investigations with a clearer path paved with rich datasets, extensive genetic resources, and robust technologies. A few of the scientific highlights of the meeting are described here, and abstracts for all presentations and posters can be found online at the Fungal Genetics Stock Center website [http://www.fgsc.net]. Understanding evolutionary relationships Setting the stage, Rytas Vilgalys (Duke University, Durham, USA) gave the opening talk on the fungal tree of life. He described the Assembling the Fungal Tree of Life project [http://ocid.nacse.org/research/aftol], which will compare sequences from seven molecular regions (approximately 10,000 base-pairs, bp) from around 1,500 species of fungi with the aim of working out the evolutionary relationships within the kingdom Fungi. He highlighted the importance of understanding broad evolutionary relationships and the sub- stantial gaps in the current state of knowledge, as organisms that have historically received the most attention and funding have been highly derived members of the tree; for example, sequenced fungal genomes almost exclusively rep- resent recently evolved lineages. This work is timely and rel- evant because it presents the opportunity to create an evolutionary framework into which our ever-increasing knowledge of fungal diversity can be integrated. Current valid estimates suggest at least 2 million fungal species, of which only some 50,000 to 70,000 have been described. The evolutionary theme continued with an overview by James Galagan (Massachusetts Institute of Technology- Broad Institute, Cambridge, USA) of comparative genomics within the ubiquitous mold genus Aspergillus, members of which are currently being sequenced. Noteworthy points that emerged from his overview include the existence of many upstream open reading frames (ORFs) in 5Ј UTRs, suggesting they are more important for regulating eukaryotic gene expression than previously suspected. Comparison of the evolutionary rate of lineage-specific rearrangements provided a quantitative picture of the forces driving eukaryotic genome evolution. Kerry O’Donnell (US Department of Agriculture, Peoria, USA) detailed the evolutionary relationships and evo- lutionary dynamics among toxin-producing Fusarium species, noting the effects of selection and neutral polymor- phism on genome structure and function. One of us (R.D.) showed the power of a completed genome sequence as a tool for dissecting biology, enumerating the insights into the pathogenesis of rice-blast disease made by the research com- munity using the recently published completed sequence of the rice-blast pathogen Magnaporthe grisea. For example, analysis of the genome revealed a large and diverse set of secreted proteins as well as an expanded family of G-protein coupled receptors. Michael Snyder (Yale University, New Haven, USA) provided a glimpse of the direction in which genome-based research is heading, reviewing his group’s research on transcriptional and phosphorylation regulatory networks in Saccharomyces cerevisiae as they compare to those of other yeasts. The two discussions truly brought to light the exciting research that we are now able to consider. Pathogenicity and pathogen-host interactions Several impressive presentations discussed the link between fungal pathogenicity and other developmental processes. Joerg Kaemper (Max Planck Institute for Terrestrial Micro- biology, Marburg, Germany) described the identification of novel DNA-binding proteins in the corn smut fungus Usti- lago maydis through whole-genome transcriptional profil- ing. These proteins, such as Rbf1, are involved in tumor formation in the host plant and filamentous growth in the fungus. Christophe d’Enfert (Institute Pasteur, Paris, France) described work on the identification of novel genes that regulate biofilm formation - a transition from yeast-like to filamentous growth - in Candida species. His work revealed one of the frustrations of the ‘candidate gene’ approach. Although transcriptional profiling revealed many candidate genes, after functional analysis only a few appeared to play an obvious role in biofilm formation. Gillian Turgeon (Cornell University, Ithaca, USA) also high- lighted some trials and tribulations of the candidate-gene approach in her work on identifying toxin-coding genes in the northern corn leaf-blight fungus, the ascomycete Cochliobolus heterostrophus. Her functional analysis of 12 potential toxin-coding genes (for polyketide synthases (PKSs) or non-ribosomal peptide synthetases (NRPSs)) revealed that only one of them, nsp6, specified a virulence factor. Significantly, functional analysis in other toxin- producing plant pathogenic ascomycetes such as Alternaria brassicicola and Fusarium graminearum also revealed that nsp6 homologs act as potent virulence factors. A poorly understood but key question in host-pathogen interactions is how avirulence gene products are delivered to the host cytoplasm. Sophien Kamoun (Ohio State University, Columbus, USA) described novel avirulence genes from the oomycete Phytophthora infestans that encode proteins with an unusual amino-terminal domain containing the core sequence RXLR. Intriguingly, a protozoan, the malaria pathogen Plasmodium falciparum, uses a similar motif to deliver proteins to red blood cells to avoid host detection. It remains to be determined whether similar motifs are found in true fungi (the oomycetes are classified in the kingdom Stramenopila). If this turns out to be the case, a combined bioinformatic and experimental approach may facilitate the identification of new avirulence genes in fungi. Fungal cell biology Fungi represent wonderful model systems for studying funda- mental principles underlying cell growth and development. The septins are key regulators of budding growth in S. cerevisiae. Michelle Momany (University of Georgia, Athens, USA) pre- sented an exciting new strategy for functional identification of septin genes that control the transition from budding to hyphal growth in Aspergillus nidulans. She demonstrated that AspC (a homolog of yeast cdc12, which encodes a protein involved in formation of the contractile ring in cytokinesis) induces S. cerevisiae to adopt a filamentous growth form, thus providing a convenient assay for such genes. Tempera- ture and light have a profound impact on fungal develop- ment, and Reinhard Fischer (University of Karlsruhe, Germany) described the presence of a phytochrome, PhsA, in A. nidulans that acts as a red-light sensor and suppresses sexual development under red light conditions. Notably, PhsA is phylogeneticlly closer to sequences in bacteria than to plants, suggesting a bacterial origin. Eukaryotic cells typically contain a single nucleus, although there are many exceptions, including fungal and cancer cells, which are multinucleate. Intriguingly, nuclear division in multinucleate fungal cells occurs asynchronously, even though the nuclei are bathed in a common cytoplasm. Amy Gladfelter (Dartmouth Medical School, Hanover, USA) pre- sented her work unraveling the underlying mechanisms of this phenomenon in the Ashbya gossypii, a filamentous fungi related to yeast, and revealed a number of surprises. Notably, the levels of cyclins and other cell-cycle regulators do not fluctuate during the cell cycle in Ashbya as is common in other eukaryotes, including the uninucleate model yeasts S. cerevisiae and Schizosaccharomyces pombe. She suggested that the cell cycle in Ashbya might be controlled through a posttranslational mechanism affecting the activity of a partic- ular cell-cycle component. This work clearly exemplifies the value of fungal systems in cell-biology research. A fundamental feature of fungal cells is their ability to fuse (anastomose) with each other. In exciting work, Nick Read (University of Edinburgh, UK) presented micrographs and movies of fusion between conidial germ tubes of Neurospora crassa, for which he has coined the term conidial anastomosis tubes (CATs). To further understand the process of anasto- mosis, he and his colleagues have developed a spectacular microscopic manipulation tool - optical tweezers - with which they can physically move organelles within hyphae, a remarkable achievement. Secondary metabolism, the production of compounds not essential for growth in culture, is thought to be integrally intertwined with development in fungi. Work with Aspergillus species has revealed a link between asexual reproduction and the production of toxic secondary metabo- lites. Interestingly, many genes involved in secondary metabolism and sporulation occur in separate clusters in the genome. Nancy Keller (University of Wisconsin, Madison, USA) presented work on the regulation of gene expression within such gene clusters. She has found that loss of LeaA, a 336.2 Genome Biology 2005, Volume 6, Issue 8, Article 336 Dean et al. http://genomebiology.com/2005/6/8/336 Genome Biology 2005, 6:336 positive regulator of secondary metabolism, results in silencing of an argB marker gene introduced into the aflatoxin gene cluster. However, loss of LeaA did not appear to suppress the expression of genes in other clusters associated with sporulation. Deletion of any of the three histone deacety- lase genes restored gene expression in the aflatoxin cluster, suggesting a role for chromatin modification in silencing, and Keller presented an elegant model for the involvement of LeaA in the epigenetic regulation of secondary metabolism. As the meeting progressed, it became evident that fungal researchers are working towards the development of a con- ceptual systems-biology framework into which the massive amounts of theoretical and empirical data can be integrated. The session on evolutionary genomics exemplified the systems view of fungal biology. Jason Stajich (Duke Univer- sity, Durham, USA) described his work on fungal intron evo- lution, which suggests an ‘early’ origin for introns, as intron distribution and density in Basidomycetes, Euascomycetes and Hemiascomycetes are best explained by recurrent rounds of intron loss. James Frasier (Duke University, Durham, USA) presented a masterful comparative study of the evolution of mating-type (MAT) loci in fungi - with an emphasis on Cryptococcus neoformans - and the sex- determining regions in animal and plant genomes, all of which show convergent evolution. His take-home message was that the MAT locus in Cryptococcus has many evolu- tionary microstrata, including the acquisition of transpos- able elements, gene conversion and chromosomal translocation, with four main steps yielding the present mating system. Ray St Leger (University of Maryland, College Park, USA) ended his talk on the role of molecular adaptation on host range with a call for the development of systems-biology concepts and experimental approaches. The meeting also saw the Thomas Hunt Morgan Medal of the Genetics Society of America presented to Robert Metzen- berg (University of California, Los Angeles, USA) for his life’s work studying the biology of N. crassa, and the presen- tation of a new award, the Metzenberg Award, created by the Neurospora policy committee in recognition of Bob Metzen- berg’s contribution to science, to Jay Dunlap (Dartmouth Medical School, Hanover, USA) for his work on circadian rhythms in N. crassa. In conclusion, the boom in fungal genome sequence data over the past few years came with high expectations for extraordinary insight into fungal biology, innovative prod- ucts, and pathogen control strategies. Several talks touched on what types of strategies are now possible, such as compu- tational approaches to deciphering genomes so as to derive biological meaning or evolutionary processes. When we meet again in two years time, we are sure to be able to learn more from fungal genomes and to search for ways to apply that knowledge towards solving animal and plant health issues as well as furthering our collective understanding of life and how it evolved. comment reviews reports deposited research interactions information refereed research http://genomebiology.com/2005/6/8/336 Genome Biology 2005, Volume 6, Issue 8, Article 336 Dean et al. 336.3 Genome Biology 2005, 6:336 . the underlying mechanisms of this phenomenon in the Ashbya gossypii, a filamentous fungi related to yeast, and revealed a number of surprises. Notably, the levels of cyclins and other cell-cycle. the activity of a partic- ular cell-cycle component. This work clearly exemplifies the value of fungal systems in cell -biology research. A fundamental feature of fungal cells is their ability. his life’s work studying the biology of N. crassa, and the presen- tation of a new award, the Metzenberg Award, created by the Neurospora policy committee in recognition of Bob Metzen- berg’s

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